Insecticidal pyridylaminidinoureas

ABSTRACT

THE INVENTION RELATES TO NEW AND USEFUL PYRIDYLAMINIDINOUREAS AND TO INSECTICIDAL COMPOSITIONS CONTAINING AT LEAST ONE OF THEM AND ALSO TO INSECTICIDAL METHODS EMPLOYING AT LEAST ONE OF THESE NEW PYRIDINE DERIVATIVES. THE COMPOUNDSOF THIS INVENTION ARE TO BE REPRESENTED BY THE FORMULA   (R-NH-C(=X)-NH-C(=NH)-)PYRIDINE   WHEREIN X IS OXYGEN OR SULFUR AND R IS ALKYL HAVNG FROM 1 THROUGH 8 CARBON ATOMS, ALKENYL HAVING FROM 3 THROUGH 6 CARBON ATOMS, CYCLOALKYL HAVING FROM 3 THROUGH 6 CARBON ATOMS, PHENYL OR BENZYL.

United States Patent Oflice 3,793,451 Patented Feb. 19, 1974 3,793,451INSECTICIDAL PYRIDYLAMINIDINOUREAS William D. Dixon, Kirkwood, Mo.,assiguor to Monsanto Company, St. Louis, M0.

N Drawing. Original application Nov. 5, 1970, Ser. No. 87,332, nowPatent No. 3,699,110. Divided and this application June 9, 1972, Ser.No. 261,179

Int. Cl. A01n 9/22 US. Cl. 424-263 20 Claims ABSTRACT OF THE DISCLOSUREThis invention relates to new and useful pyridylaminidinoureas and toinsecticidal compositions containing at least one of them and also toinsecticidal methods employing at least one of these new pyridinederivatives. The compounds of this invention are to be represented bythe formula NH X Lela-R 1 1 wherein X is oxygen or sulfur and R is alkylhaving from 1 through 8 carbon atoms, alkenyl having from 3 through 6carbon atoms, cycloalkyl having from 3 through 6 carbon atoms, phenyl orbenzyl.

This is a division, of application Ser. No. 87,332, filed Nov. 5, 1970now U.S. Pat. No. 3,699,110.

This invention relates to new and useful pyridylaminidinoureas and toinsecticidal compositionscontaining at least one of them and also toinsecticidal methods employing at least one of these new pyridinederivatives. The compounds of this invention is to be represented by theformula NH X ii-N-ii-N-R 1 1 wherein X is oxygen or sulfur and R isalkyl having from 1 through 8 carbon atoms, alkenyl having from 3through 6 carbon atoms, cycloalkyl having from 3 through 6 carbon atoms,phenyl or benzyl. The terms benzyl and phenyl include substituted andunsubstituted aryl groups. Representative ring substitutents are halo,nitro, trichloromethyl, methyl and the like.

The alkyl group in these compounds can be methyl, ethyl, normal propyl,isopropyl, normal butyl, secondary butyl, tertiary butyl, normal pentyl,isopentyl and the various forms of hexyl, heptyl and octyl.

The compounds of the present invention can be readily prepared by thereaction of a pyridylamidine hydrochloride with a substantiallyequimolar portion of an appropriately substituted isocyanate orisothiocyanate in a suitable solvent and in the presence oftriethylamine. Suitable solvents include chloroform, acetonitrile,tetrahydrofuran and the like. The reaction which is exothermic is mostconveniently conducted at room temperature but can be carried out at anytemperature up to the boiling point of the solvent. The pyridylamidinehydrochloride used as a starting material in the reaction is obtained ina conventional manner by the addition reaction of a cyanopyridine withmethanol to provide the corresponding imidate which is then converted tothe amidine hydrochloride salt by treatment with ammonium chloride. Thepreparation of the compounds of this invention is illustrated by thefollowing examples. In these examples and throughout the specificationall proportions are expressed in parts by weight unless otherwisedesignated.

EXAMPLE 1 1- (3 ,4-dichlorophenyl -3- (2-pyridylformimidoyl) 2-thioureaAbout 160 parts of nicotinamidine hydrochloride, parts of triethylamineand 2,000 parts chloroform were stirred together in a suitable reactionvessel equipped with a condenser and a thermometer. About 200 parts of3,4-dichlorophenylisothiocyanate were then added and agitation wascontinued until completion of the reaction. Since the reaction isexothermic the temperature of the reaction medium increased to about 35C. from an initial temperature of approximately 20 C. The product wasobtained in the form of a yellow precipitate which was removed from thereaction medium by filtration, and recrystallized from acetone. Thecompound had a melting point of 184-185 C. and gave the followinganalysis:

Calcd for C H Cl N S (percent): C, 48.01; H, 3.10; N, 17.23. Found(percent): C, 48.01; H, 3.06; N, 17.35.

EXAMPLE 2 M.P., C.

1 (3,4 dlchlorophen 1) 3 (2 pyridylforminidoybureann 156-158 1-(l-chlorophenyl)-3-&-pyridy1formimm1doyl)urea 158-1611-butyl-3-picolinimidoylurea 705275155l-methyl-B-picolinimidofilthiourea 1-(p-nitrophenyl)-3-pic0'nimidoylthiourea.. 195-196 1-butyl-3-picolinimidoylthiourea.--.. 50-51.5 l-ethyl-3-picolinimidoylthiourea. 56. 5-591-(tert-butyl)-3-picolinimidoylthioure 137. 5-140. 5l-heptyl-3-picolinimldoylth1ourea 57-60 l-allyl-3-picolinimidoylth1ourea 49-521-(m-bromophenyD-3-picolinimidoylthiourea -147 1-(p-bromophenyD-3-icolinimidoylthiourea 170-171 1-(o-tert-butyl-o-tolylRii-pieolininndo1thiourea.. 139. 5-141. 5 l-(m-chlorophenyl)-3-picolinimidoylt iourea145. 5-147. 5 1-(p-chloropheuyl)-3-picolinirnidoylthiourea. -1611-(3,4-diohlorobenzyl)-3-picolinimidoylthiour 124-127I-pioolinimidoyl-El-(p-tolyDthiourea 132-134 1 picollnimidoyl 3(u.,n.,n.-l; 'fluoro o tolyl) 2 thiourea- 113-116 Do- 145-1471-phenyl-3-picolinimidoylurea 135-136 l-picolinimidoyl-3-p-tolylurea 129-13! 1- henyl-3-plcolinimidoylthiourea 125-137 l-gt-ohlorophenl)-3-(3-pyridylformimidoyDure 189-191 1-(3,4-diehloropenyl)-3-(S-pyridylformirnidoyl)urea 187-189l-(p-tolyl)-3-(3-pyridlfonnimidoyl)urea 178-180 l-phen l-3-(3-pyridyormimidoyD-Z-thiourea 127-129 1-(3,4-chlorophenyl)-3-(3-pyrldylformimidoyl)-2-thiourea-- 178-1801-methyl-3-nicotinimidoyl-2-thiourea 138-1401-butyl-3-(3-pyridylformi1nidoyl)-2-thiourea 85-87l-ethyl-S-nicotinimidoylthlourea 113-117I-nicotinimidoyl-3-(p-nitrophenyDthiourea 261-265l-heptyl-3-nieotinimidoylthiourea 52-55l-eyclohexyl-ii-nicotinimidoylthiourea 160-161. 5 1- (m-bromophenyl)-3-nicotinimidoylthiourea. 154. 5-157 1- (p-bromophenyl)-3-nicotinimidoylthiourea. 181-182. 5 l-nicotinimidoyl-3-p-tolylthiourea159-161 1-(3,4-dichlorobenzyl)-3-nicotinimidoylthiourea. 157. 5-1601-nicotinimidoy1-3-(a,a,a-trifluoro-o-toly1)-2-thioure -1661-(3-butoxypropyl)-3-nicotinimidoylthioureal-nieotinhnidoyl-ti-phenylurea 168-169 l-butyl-li-nicotinimidoylurea99-102 l-methyl-3-nicotinirnidoylurea 151-154l-isonicotinimidoyl-li-methylthiourea 136-138. 5l-isonicotirdmidoyl-3-pheny1thiourea. 162-1641-butyl-3-isonicotinimidoylurea 88-921-isonicotlnirnidoyl-B-p-tolylurea. -1771-(3,4-dichlorophenyl)-3-isonicoti -196. 51-isonicotinimidoyl-3-methylurea 183-185 1 No B.P. listed.

The terms insec and insecticide are used herein in their broad commonusage to include spiders, mites, ticks, and like pests which are not inthe strict biological sense classed as insects. Thus, the term insect isused to refer not only to those small invertebrate animals (Diabroticavirgifera) 1 phenyl 3 picolinimidoylthio-' urea was incorporated intosoil containing corn root segments and the soil was infested withwestern corn rootworm larvae. The soil was then maintained for 48 hoursat 25 C. and the larval mortality determined. A 100% mortality rate wasobtained with soil containing 6 ppm. ofthis compound.

In order to illustrate the activity of the present compounds against thesouthern corn rootworm, the following procedure was followed:

To a growth pouch, (diSPo Seed-Pak growth pouch,

Catalogue No. B1220, of Scientific Products Division of AmericanHospital Supply Corporation, 'Evanston, Ill.) in an upright position isadded 20 m1. of distilled water. Thereafter is added 0.1-ml. of anacetone solution of known concentration in percent by weight of acompound of this invention (for example a 0.1 ml. of a 0.1% by weightacetone solution of the compound provides a con centration of 5.0 ppm.thereof). In the trough of the pouch formed ,by the paper wick thereofare placed two corn seeds (Zea mays, Hybrid U.S. 13) about one inchapart. Thereupon to the trough and between the seeds is added 8 to 12ready-to-hatch eggs of the southern corn rootworm (Diabroticaundecimpunctata howardi) which eggs were washed (with distilled water)free of the soil in which they were incubated at room temperature for 21days immediately prior to their placement in the trough. The so-cha'rgedgrowth pouch is then placed in an upright position in an incubatormaintained at.80 F. and 70% relative humidity for 14 days. Immediatelythereafter the growth pouches are removed and the extent of kill inpercent of the corn rootworm larvae observed. At a concentration of ppm,a 100% killw'as observed with 1-phenyl-3-picolinimidoylthiourea and atthe same concentration a 60% mortality rate was obtained with 1 (ptolyl) 3 (3-pyridylformimidoyl)urea. I

As shown below the compounds of this invention are also effective incombatting mosquitoes.

A base solution of the compound to be evaluated is prepared bydissolving 1.0 gram thereof in sufiicient acetone to provide a 0.10% byweight solution thereof. Then 0.10. ml. of this actone solution ispipetted into a 25 x 200 mm, culture tube cointainingsufficientdistilled water to pro-F vide a concentration of 2 ppm. of the compound.The tube is stoppered and shaken vigorously to fa cilitate completemixing of its contents. Thereupon approximately 25 early instar yellowfever mosquito larvae (Aedes aegypti) are transferred to the tube withthe aid of a pipette. Thelarvae are then held in the tube at 25 C. forseven days, at the end of which time mortality observations are taken.At a concentration of 2 p.p.rn., 100% kills were obtained with 1nicotinimidoyl 3 p tolylthiourea, l-(3,4-dichlorobenzyl) 3nicotinimidoylthiourea, 1 (p chlorophenyl) 3 picolinimidoylthiourea andwith 1-(3,4-dichlorobenzyl) 3 picolinimidoylthiourea.

The term dispersed is used herein in its widest possible sense.Particles of the compounds may be molecular in size and held in truesolution in a suitable organic solvent, or the particles may becolloidal in size and distributed throughout a liquid phase in the formof suspensions or emulsions, or in the form of particles held insuspensions by wetting agents. The term includes particles which aredistributed in a semi-solid viscous carrier such as petrolatum or soapor other ointment base in which they may be actually dissolved in thesemi-solid or held in suspension in the semi-solid with the aid ofsuitable wetting or emulsifying agents. The term dispersed also meansthat the particles ina'y be mixed with and distributed throughout asolid carrier providing a mixture in particulare form, e.g. pellets,granules, powders, or dusts. The term "dispersed also includes mixtureswhich are suitable for use as aerosols including solutions, suspensions,or emulsions of the compounds of the invention in a carrier such asdichloro-difluoromethane and the like which boil below room temperatureat atmospheric pressure.

The expression extending agent as used herein includes insecticidaladjuvants and any and all of the substances in which the compounds ofthis invention are dispersed. It includes, therefore, the solvents of atrue solution, the liquid phase of suspensions, emulsions or aerosols,the semi solid carrier ,of ointments and the solid phase of particulateso1ids,'e.g., pellets, granules, dusts and powders.

The exact concentration of the compounds of this inv'ention employed incombatting or controlling insects pests can vary considerably providedthe required dosage (i.e., toxic or lethal amount) thereof is suppliedto the pests or to the environment of the pests. When the extendingagent is a liquid or mixture of liquids (e.g., as in solutions,suspensions, emulsions, or aerosols) the concentration of the activecompound employed to supply the desired dosage generally will be in therange of 0.0001 to percent by weight. When the extending agent is asemi-solid or solid, the concentration of the insecticide employed tosupply the desired dosage generally will be in the range of 0.1 to 75percent by weight. From a practical point of view, the manufacturer mustsupply the user with a concentrate in such form that, by merely mixingwith water or solid extender (e.g., powdered clay or talc) or otherlow-cost material available to the user at the point of use. he willhave an easily prepared insecticidal spray or particulate solid. In sucha concen-.

trate composition, the insecticide generally will be present in aconcentration of 5 to 95 percent by weight, the residue being any one ormore of the well-known insec ticidal adjuvants, such as the varioussurface active agents (e.g., detergents, a soap or other emulsifying orwetting agent), surface-active clays, solvents, diluents, carrier media,adhesives, spreading agents, humectants, and the like.

The are a large number of organic liquids which can beused alone or incombination for the preparation of solutions, suspensions or-emulsionsof the compounds of this invention. For example, isopropyl ether,acetone,

I methyl ethyl ketone, dioxane, cyclohexanone, carbon tetrathereof canbe 'replaced by such low molecular weight aliphatic 'hydrocarbons asdipentene, diisobutylene, propylene trimer, and the like or suitablepolar organic liquids such as the aliphatic ethers and the-aliphaticketones containing not more than about 10 carbon atoms as exemplified byacetone, methyl ethyl ketone, diisobutyl ketone, dioxane, isopropylether, and the like.

The insecticides of this invention. can be supplied to the insect pestsor to the environment of the insect pests in. the form-of-ernulsions orsuspensions. Emulsions or suspensions are prepared by dispersing thecompounds either per se or in the form of anorganic solution thereof inwater with'the aid of a water-soluble surfactant. The term surfactant?as employed herein isas used in volume II of Schwartz, 'Perry and BerchsSurface Active Agents and Detergents (.1958, Interscience Publishers,Inc., New York) in place of the expression emulsifying agent to connotegenerically the various emulsifying agents, dispersing agents, wettingagents and spreading agents that are adapted to be admixed with theactive compounds of this invention in order to secure bette1' wettingand spreading of the active ingredients 111 the water vehicle or carrierin which they are insoluble through lowering the surface tension of thewater (see also Frear Chemistry of Insecticides, Fungicides andHerbicides, second edition, p. 280). These surfactants include thewell-known capillary-active substances which may be anionic, cationic,or nonionic which are described in detail in volumes I and II ofSchwartz, Perry and Berchs Surface Active Agents and Detergents (1958,Interscience Publishers, Inc., New York) and also in the November 1947issue of Chemical Industries (PP. 811- 824) in an article entitledSynthetic Detergents by John W. McCutcheon and also in the July, August,September and October 1952 issues of Soap and Sanitary Chemicals underthe title Synthetic Detergents. The disclosures of these articles withrespect to surfactants are incorporated in this specification byreference in order to avoid unnecessary enlargement of thisspecification. The preferred surfactants are the water-soluble anionicnoniom'c surface-active agents set forth in U .S. Pat. 2,846,398 (issuedAug. 5, 1958). In general, a mixture of watersoluble anionic andwater-soluble nonionic surfactants is preferred.

The compounds of this invention can be dispersed by suitable methods(e.g. tumbling or grinding) in solid extending agents either of organicor'inorganic nature and supplied to the insect pests environment inparticulate form.. Such solid materials, include for example, tricalciumphosphate, calcium carbonate, kaolin, bole, kieselguhr, talc, bentonite,attapulgite, fullers earth, pyrophillite, diatomaceous earth, calcinedmagnesia, volcanic ash, sulfur and the like inorganic solid materials aswell as organic materials such as powdered cork, corn husks, corn cobs,powdered wood, and powdered walnut shells. The preferred solid carriersare the adsorbent clays, e.g., diatomaceous earth. These mixtures can beused for insecticidal purposes in the dry form, or by addition ofwater-soluble surfactants or wetting agents the dry particulate solidscan be rendered wettable by water so as to obtain stable aqueousdispersions or suspensions suitable for use as sprays. When used in thedry form, the preferred carrier is diatomaceous earth, and theconcentration of the present pesticides on this carrier is normallybetween about and 50% by weight of the total composition. For mostpractical purposes, the concentration is normally maintained betweenabout 20 and 30%. A typical composition contains about 25% of apesticide of the present invention and about 75% diatomaceous earth.

For special purposes the compounds of this invention can be dispersed ina semi-solid extending agent such as petroleum or soap (e.g. sodiumstearate or oleate or palmitate or mixtures thereof) with or without theaid of solubility promoters and/or surfactants or dispersing agents.

In all of the forms described above, the dispersions can be providedready for use in combatting insect pests or they can be provided in aconcentrated form suitable for mixing with or dispersing in otherextending agents. As illustrative of a particularly useful concentrateis an intimate mixture of a compound of this invention with awater-soluble surfactant in the weight proportions of 0.1 to parts ofsurfactant with suflicient sulfinate to make 100 parts by weight. Such aconcentrate is particularly adapted to be made into a spray forcombatting the insect pests by the addition of water thereto.

Another useful concentrate adapted to be made into a spray forcombatting a variety of insect pests is a solution (preferably asconcentrated as possible) of a compound of this invention in an organicsolvent therefor. The said liquid concentrate preferably containsdissolved therein a minor amount (e.g. 0.5 to 10 percent by weight ofthe weight of the new insecticidal agent) of a water-soluble surfactant(or emulsifying agent).

Of the surfactants aforementioned in preparing the various emulsifiable,wettable or dispersible compositions or concentrates of this invention,the anionic and nonionic surfactants are preferred. Of the anionicsurfactants, the particularly preferred are the well-known watersolublealkali metal alkylaryl sulfonates as exemplified by sodium decylbenzenesulfonate and sodium dodecylbenzene sulfonate. Of the nonionicsurfactants, the particularly preferred are the water-solublepolyoxyethylene derivatives of alkylphenols (particularlyisooctylphenol) and the water-soluble polyoxyethylene derivatives of themono-higher fatty acid esters of hexitol anhydrides (e.g. sorbitan).These materials in general contain 15 to 30 moles of ethylene oxide permole of the hexitol anhydride or the alkylphenol.

The compositions of this invention can also contain other additamentssuch as fertilizers and pesticides used as, or in combination with, thecarrier materials. [For example, the insecticides useful in combinationwith the above-described compounds include parathion, methyl parathion,pyrethrine, nicotine, aldrin, chlordane, heptachlor, toxaphene,malathion, 2-isopropoxyphenyl N-methylcarbamate, 0,0,0,0 tetramethyl 0,0thiodo pphenylene phosphorothioate, dimethyl phosphate of 3-hydroxy-N-methyl-cis-crotonamide, fenthion, carbofuran, mirex, DDT,dicofol, methoxychlor, dichlorvos, demeton, dimethoate, carbophenothion,ronnel, carbaryl, azinphosmethyl, methomyl, aldicarb and the like.

In controlling or combatting insect pests the compounds of thisinvention either per se or compositions containing them are supplied tothe insect pests or to their environment in a lethal or toxic amount.This can be done by dispersing the new insecticidal agent orinsecticidal composition comprising same in, on or over agriculturalsoil or other growth media or other media infested with insect pests orattractable to the pests for habitational or sustenance or propagationalpurposes, in any conventional fashion which permits contact between theinsect pests and the compounds of this invention. Such dispersing can bebrought about by applying sprays, dips or particulate solid compositionsto a surface infested with the insect pests or attractable to the pests.Also for sub-surface application such dispersing can be carried out bysimply mixing the new insecticidal agent per se or insecticidal spray orparticulate solid compositions comprising same with the infestedenvironment or with the environment the insect pests frequent, or byemploying a liquid carrier for the new insecticidal agent to accomplishsub-surface penetration and impregnation therein.

While this invention has been described with respect to certainembodiments, it is to be understood that it is not so limited and thatvariations and modifications thereof obvious to those skilled in the artcan be made without departing from the spirit and scope thereof.

What is claimed is:

1. An insecticidal composition comprising an insecticidal adjuvant andan insecticidal'ly effective amount of a compound of the formula whereinX is oxygen or sulfur and R is alkyl having from 1 through 8 carbonatoms, alkenyl having from 3 through 6 carbon atoms, cycloalkyl havingfrom 3 through 6 carbon atoms, phenyl or benzyl with the proviso thatthe floating radical is not attached to the 2 or 6 position when theterm X represents sulfur and the term R represents unsubstituted phenyl.

2. The composition of claim 1 in which R-is benzyl or phenyl. Y

3. The composition of claim 1 in which R isvalkyl.

4. The composition of claim 1 in which R is benzyl or' phenyl andX issulfur.

5. The composition of claim 1 in is 1-phenyl-3-picolinimidoylthiourea.th,

6. The composition of claim 1 in which the compound is1-(p-tolyl)-3-(3-pyridylformimidoyl)urea.

7. The composition'of claim 1 in which the compound 7 10 is1-nicotinimidoyl-3-p-tolylthiourea. v 8. The composition of claim 1 inwhichthe compound is 1-(3,4-dich1orobenzyl)-3 nicotinimidoylthiourea.

9. The composition of claim 1 in which: the compound is1-(p-chlorophenyl)fi picolinimidoylthiourea.

. 10. The compositionof claim 1 in whichthe compound is1-(3,4-dichlorobenzy1)-3-picolinimidoylthiourea. t

11. A method of killing insects which comprises bringing into contactwith the insects an insecticidally eifective amount of a compound of theformula .t

wherein X is oxygen or sulfur and R is alkyl having from. 1 through 8carbon atoms, alkenyl having from 3 through 6 can-bon atoms, cycloalkylhaving from 3 through 6 carbon atoms, phenyl or benzyl.

which the compound; 5

12. The method of claim 11 in which R is benzyl or phenyl.

13.,The method of claim 11 in which R is alkyl.

14. The method of claim 11 in which R is benzyl or phenyl and X issulfur.

15. The method of claim 11 in which thecompoundl I References Cited 1UNITED STATES PATENTS 3,699,1l0 10/1972 Dixon 260294. 8 E

OTHER REFERENCES Chemical Abstracts 52:13713H (1958).

ALBERT T. MEYERS, Primary Examiner L. SCHENKMAN, Assistant Examiner US.Cl. X.R. 424-266

